Certain esters of the 3,5-dichloro; 3,5-dibromo-; and 3,5-diiodo-4-hydroxybenzonitriles, also known respectively as chloroxynil, bromoxynil and ioxynil are extensively used as broadleaf weed herbicides, particularly in crop-growing areas.
Examples of such esters are those formed from the 3,5-dichloro-, 3,5-dibromo-, or 3,5-diiodo-4-hydroxybenzonitriles and unsubstituted or halogenated aliphatic, cycloaliphatic or aromatic acids, such as trichloroacetic, propionic, 2,2-dichloropropionic, n-butanoic, n-octanoic, 2-ethylhexanoic, cyclohexylcarboxylic, benzoic and benzenesulfonic acids.
Three synthesis of these herbicides from the dihalohydroxybenzonitriles have been described in the prior art.
U.S. Pat. No. 3,592,626 (Heywood et al) details two methods. According to one, the 3,5-dihalo-4-hydroxybenzonitrile is reacted with an organic anhydride in the presence of a condensing agent, such as concentrated sulfuric acid or a sodium or potassium salt of the corresponding organic acid. According to the other method, the benzonitrile derivative is reacted with an acid halide, e.g., the chloride, in the presence of a tertiary base, e.g., pyridine, or in the presence of a quaternary ammonium salt, e.g. tetralkylammonium chloride.
Both of these methods have disadvantages and shortcommings.
In the anhydride method, only one-half of the acid equivalent of the anhydride is reacted with the hydroxybenzonitrile, the other half is converted into free acid which must be removed from the reaction mixture and is essentially a waste product. Also, the removal of the condensing agent, sulfuric acid or alkali salt of the organic acid, needs additional processing and causes extra expenses when the ester of the benzonitrile is needed in a purified form.
The use of tertiary bases, such as pyridine, usually in excess, in the second method mentioned is expensive and complicates the synthesis process for the following reason. Most of the base has to be recovered for reuse, necessitating an appropriate separation step such as distillation. The portion of the base which served as acceptor for the hydrogen chloride formed requires other processing steps as it has to be separated from the ester product.
The variant of the acid chloride method carried out in the presence of quaternary salts has the disadvantage of employing these rather costly salts. Their direct recovery for reuse is expensive, if not impossible and even the separation of these salts from the product ester involves such steps as addition of solvent, neutralization and crystallization.
U.S. Pat. No. 3,671,556 (Goldstick) discloses a third method for the preparation of esters of 3,5-dihalo-4-hydroxybenzonitriles. It is taught that the esters can be formed by the direct reaction of the hydroxybenzonitrile derivatives with the appropriate acid halides, if the dry, solid hydroxybenzonitrile is gradually added to a slight excess of the liquid acid halide, e.g. capryloyl chloride, kept at a temperature above 120.degree. C. The reaction need not be carried out in the presence of any base, acid acceptor, catalyst or condensing agent, however, it is suggested that in the case where the acid chloride is unusually viscous or high-melting, a solvent can be used.
All of the above processes, of course, anticipate preparing the esters from a previously isolated dihalohydroxybenzonitrile reactant.
With regard to the preparation of these dihalohydroxybenzonitrile reactants, E. Muller et al, Chem. Ber. 92, 2278(1959) teaches that p-hydroxybenzonitrile should be dissolved in methanol and glacial acetic acid and then treated with bromine. The product is then poured into an aqueous methanolic solution of NaHSO.sub.3.
Luckenbaugh (U.S. Pat. No. 3,349,111) discloses that 3,5-dibromo-4-hydroxybenzonitrile can be prepared by reacting an aqueous suspension of p-hydroxybenzonitrile with aqueous alkali metal hydroxide or aqueous alkali metal carbonate; reacting the mixture with bromine; further reacting this mixture with chlorine; then acidifying the mixture and finally filtering to obtain the product. An alternative process eliminates the base.
All of the prior art processes require that the dihalohydroxybenzonitrile intermediate be isolated usually by filtration, from the bromination reaction medium before esterification can be realized because the prior art bromination solvent/reaction media are incompatable with the prior art esterification/solvent media. This necessitates, at least at some stage, removal of the intermediate dihalohydroxybenzonitrile from the bromination reactor before the esterification process.